Proteomics plus genomics approaches in primary immunodeficiency: the case of immune dysregulation, polyendocrinopathy, enteropathy, X‐linked (IPEX) syndrome

• Published in: Clinical and experimental immunology 2012-01, Vol.167 (1), p.120-128
• Main Authors: Zennaro, D., Scala, E., Pomponi, D., Caprini, E., Arcelli, D., Gambineri, E., Russo, G., Mari, A.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Allergens; Analytical, structural and metabolic biochemistry; Biological and medical sciences; CD26 antigen; CD7 antigen; Cow's milk; DNA microarrays; Endocrine System Diseases - blood; Endocrine System Diseases - genetics; Endocrine System Diseases - immunology; Flow cytometry; Food hypersensitivity; Food Hypersensitivity - blood; Food Hypersensitivity - genetics; Food Hypersensitivity - immunology; Forkhead protein; Forkhead Transcription Factors - deficiency; Forkhead Transcription Factors - genetics; Foxp3 protein; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression Profiling; Genes, X-Linked; Genetic Diseases, X-Linked - blood; Genetic Diseases, X-Linked - genetics; Genetic Diseases, X-Linked - immunology; genomics; Genomics - methods; Genotype & phenotype; Helper cells; Humans; Immune system; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunodeficiency; Immunoglobulin E; Immunoglobulin E - immunology; Immunologic Deficiency Syndromes - blood; Immunologic Deficiency Syndromes - genetics; Immunopathology; Immunophenotyping; Immunoregulation; IPEX syndrome; Lymphocytes; Lymphocytes B; Lymphocytes T; Lymphoma, Large B-Cell, Diffuse - genetics; Lymphoma, Large B-Cell, Diffuse - pathology; Male; Medical sciences; Mutation; Oligonucleotide Array Sequence Analysis; Peripheral blood; Proteomics; Proteomics - methods; Receptors, Antigen, T-Cell, alpha-beta - genetics; RNA; Sequence Analysis, DNA; specific IgE; T cell receptors; T-cell receptor; T-Lymphocyte Subsets - immunology; Tonsillar Neoplasms - genetics; Tonsillar Neoplasms - pathology; Translational Studies; Triticum aestivum; X chromosome; Young Adult
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1111/j.1365-2249.2011.04492.x

Summary Immune dysregulation, polyendocrinopathy, enteropathy, X‐linked (IPEX) is a rare syndrome due to a mutation in the forkhead box protein 3 gene (FOXP3) leading to an impaired regulatory T cell (Treg) activity associated both with skewed T helper type 2 (Th2) response and autoreactive phenomena. The purpose of this study was to describe a combined proteomics and genomics approach to comprehensively evaluate clinical and immunological phenotypes of patients affected by IPEX. T cell receptor (TCR)‐Vβ repertoire and peripheral blood lymphocytes phenotype from three brothers affected by IPEX were studied by flow cytometry. Specific immunoglobulin (Ig)E were evaluated by means of an allergenic molecules microarray [immuno solid‐phase allergen chip (ISAC)]. Total RNA was extracted and hybridized to Affymetrix oligonucleotide arrays to obtain quantitative gene‐expression levels. No FOXP3 protein was detectable within CD127‐CD25highCD4+ T cells from peripheral blood. A T cell‐naive phenotype (CD62L+CD45R0‐) associated with a reduction of both CD26 and CD7 expression and a TCR‐Vβ 8 and 22 family expansions were found. B lymphocytes were mainly CD5+ (B1) cells expressing a naive phenotype (tcl1+CD27‐). The three IPEX patients had severe food allergy and specific IgE reactivity to cow's milk allergens, a hen's egg allergen and a wheat allergen. Gene expression profile analysis revealed a dysregulation associated mainly with Th1/Th2 pathways. The multiplexing evaluation reported in this study represents a comprehensive approach in the assessment of genetic conditions affecting the immune system such as the IPEX syndrome, paving the way for the development of diagnostic tools to improve the standard clinical and immunological profiling of the disease.